TY - JOUR
T1 - Liver receptor homolog-1 regulates mouse superoxide dismutase 2
AU - Lee, Jun Su
AU - Bae, Sijeong
AU - Kang, Hye Suk
AU - Im, Seung Soon
AU - Moon, Young Ah
N1 - Funding Information:
This study was supported by grants from the Korea Research Foundation, Medical Research Center (2014R1A5A2010008), and an NRF grant funded by the Korea Government (MSIP) (2016R1A2B4008516) to Im SS. This study was also supported by a New Faculty Grant from Inha University (53355-01, Moon YA).
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/7/29
Y1 - 2017/7/29
N2 - Liver receptor homolog-1 (LRH-1) is a nuclear receptor that plays an important role in the regulation of bile acid biosynthesis, cholesterol reverse transport, steroidogenesis, and exocrine pancreatic enzyme production. In the current study, previously published data from a genome wide analysis of LRH-1 binding in the liver were re-analyzed to identify new LRH-1 targets and propose new roles for LRH-1 in the liver. Superoxide dismutase 2 (Sod2) was identified, which contains putative LRH-1 binding sites in the proximal promoter. When hepatocytes were treated with the LRH-1 agonist RJW101, Sod2 expression was dramatically increased and reactive oxygen species (ROS) production, which was induced by a high concentration of palmitate, was significantly reduced. A LRH-1 binding site was mapped to −288/−283 in the Sod2 promoter, which increased Sod2 promoter activity in response to LRH-1 and its agonist. LRH-1 binding to this site was confirmed using a chromatin immunoprecipitation assay. These results suggest that Sod2 is a target gene of LRH-1, and that LRH-1 agonists can mediate a reduction in ROS production and oxidative stress driven by an excess of fatty acids, as exhibited in nonalcoholic fatty liver disease.
AB - Liver receptor homolog-1 (LRH-1) is a nuclear receptor that plays an important role in the regulation of bile acid biosynthesis, cholesterol reverse transport, steroidogenesis, and exocrine pancreatic enzyme production. In the current study, previously published data from a genome wide analysis of LRH-1 binding in the liver were re-analyzed to identify new LRH-1 targets and propose new roles for LRH-1 in the liver. Superoxide dismutase 2 (Sod2) was identified, which contains putative LRH-1 binding sites in the proximal promoter. When hepatocytes were treated with the LRH-1 agonist RJW101, Sod2 expression was dramatically increased and reactive oxygen species (ROS) production, which was induced by a high concentration of palmitate, was significantly reduced. A LRH-1 binding site was mapped to −288/−283 in the Sod2 promoter, which increased Sod2 promoter activity in response to LRH-1 and its agonist. LRH-1 binding to this site was confirmed using a chromatin immunoprecipitation assay. These results suggest that Sod2 is a target gene of LRH-1, and that LRH-1 agonists can mediate a reduction in ROS production and oxidative stress driven by an excess of fatty acids, as exhibited in nonalcoholic fatty liver disease.
KW - Liver receptor homolog-1
KW - Nonalcoholic fatty liver disease
KW - Reactive oxygen species
KW - Superoxide dismutase 2
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U2 - 10.1016/j.bbrc.2017.05.144
DO - 10.1016/j.bbrc.2017.05.144
M3 - Article
C2 - 28552526
AN - SCOPUS:85019983584
SN - 0006-291X
VL - 489
SP - 299
EP - 304
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -